Construction of rat model with phenytoin-resistant mesial temporal lobe epilepsy_Journal of Epilepsy

Authors：

FANG Ziyan ^1,2 , WU Fengchun ^1,2 , CHEN Shuda ³ , QIN Jiaming ⁴ ,  NING Yuping ^1,2 ,  ZHOU Liemin ^3,4

1. Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou 510370, China;
2. Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China;
3. Department of Neurology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China;
4. Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China;

Corresponding?author：

NING Yuping, Email: ningjeny@126.com; ZHOU Liemin, Email: lmzhou56@163.com

Keywords：

Li-pilocarpine; Mesial temporal lobe epilepsy; Drug-resistant epilepsy; Microdialysis; Phenytoin; P-glycoprotein

DOI：

10.7507/2096-0247.20190004

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objectives The purpose of this study is to verify the phenytoin-resistant mesial temporal lobe epilepsy (MTLE) induced by Li-pilocarpine and screened by antiepilepsy drug (AEDs). Methods The rats with MTLE were induced by Li-pilocarpine, which were screened by effect of phenytoin treatment monitored by vedio-EEG. The living microdialysis technology was used for verification of drug concentration in brain of drug-resistant and drug-responsive rat model, and the P-glycoprotein expression was detected by immunohistochemical method. Results Sixteen rats with chronic MTLE were successfully induced in total 30 rats, among which, 6 drug-resistant rats with MTLE were screened. The brain/plasma ratio of area under the curve in drug-resistant rats was significantly lower than that of drug-responsive rats (0.15±0.03 vs. 0.28±0.05, P<0.05). In addition, the P-glycoprotein expression in brain of drug-responsive rats was obviously higher than that of drug-responsive rats (P<0.05). Conclusions The low concentration of phenytoin in drug-resistant rat model with MTLE was verified that might be related to the over-expressed P-glycoprotein in brain.

Citation： FANG Ziyan, WU Fengchun, CHEN Shuda, QIN Jiaming, NING Yuping, ZHOU Liemin. Construction of rat model with phenytoin-resistant mesial temporal lobe epilepsy. Journal of Epilepsy, 2019, 5(1): 21-25. doi: 10.7507/2096-0247.20190004 Copy

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7.	Volk HA, Loscher W. Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures. Brain, 2005, 128(Pt 6): 1358-1368.
8.	方子妍, 郭彩鳳, 吳逢春, 等. 普朗尼克 P85 修飾的苯妥英鈉納米粒對顳葉內側癲癇大鼠模型的腦靶向作用. 中國神經精神疾病雜志, 2017, 43(06): 356-361.
9.	方子妍, 郭彩鳳, 吳逢春, 等. Tariquidar 提高苯妥英鈉在顳葉內側癲癇模型鼠腦中的分布. 臨床醫學工程, 2017, 24(06): 762-764.
10.	Fang ZY, Chen SD, Chen YS, et al. Pluronic P85 enhances the delivery of phenytoin to the brain versus verapamil in vivo. Latin American Journal of Pharmacy, 2014, 33(5): 812-818.
11.	Fang Z, Chen S, Qin J, et al. Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy. Biomaterials, 2016, 97: 110-121.
12.	Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol, 1972, 32(3): 281-294.
13.	Loscher W. Animal Models of seizures and epilepsy: past, present, and future role for the discovery of antiseizure drugs. Neurochem Res, 2017, 42(7): 1873-1888.
14.	劉陽, 韓春雷, 孟凡剛. 匹羅卡品癲癇模型研究進展. 中華神經外科雜志, 2014, 30(1): 88-90.
15.	陳樹達, 陳子怡, 方子妍, 等. 普朗尼克 P85 與維拉帕米對苯妥英鈉腦靶向分布的比較. 中山大學學報(醫學科學版), 2014, 35(2): 161-168.

1. Kwan P and Brodie MJ. Definition of refractory epilepsy: defining the indefinable?. Lancet Neurol, 2010, 9(1): 27-29.
2. Golyala A and Kwan P. Drug development for refractory epilepsy: The past 25 years and beyond. Seizure, 2017, 44: 147-156.
3. Santulli L, Coppola A, Balestrini S, et al. The challenges of treating epilepsy with 25 antiepileptic drugs. Pharmacol Res, 2016, 107: 211-219.
4. Banerjee Dixit A, Sharma D, Srivastava A, et al. Upregulation of breast cancer resistance protein and major vault protein in drug resistant epilepsy. Seizure, 2017, 47: 9-12.
5. Hartz AM, Pekcec A, Soldner EL, et al. P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy. Mol Pharm, 2017, 14(4): 999-1011.
6. Feldmann M and Koepp M. ABC Transporters and Drug Resistance in Patients with Epilepsy. Curr Pharm Des, 2016, 22(38): 5793-5807.
7. Volk HA, Loscher W. Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures. Brain, 2005, 128(Pt 6): 1358-1368.
8. 方子妍, 郭彩鳳, 吳逢春, 等. 普朗尼克 P85 修飾的苯妥英鈉納米粒對顳葉內側癲癇大鼠模型的腦靶向作用. 中國神經精神疾病雜志, 2017, 43(06): 356-361.
9. 方子妍, 郭彩鳳, 吳逢春, 等. Tariquidar 提高苯妥英鈉在顳葉內側癲癇模型鼠腦中的分布. 臨床醫學工程, 2017, 24(06): 762-764.
10. Fang ZY, Chen SD, Chen YS, et al. Pluronic P85 enhances the delivery of phenytoin to the brain versus verapamil in vivo. Latin American Journal of Pharmacy, 2014, 33(5): 812-818.
11. Fang Z, Chen S, Qin J, et al. Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy. Biomaterials, 2016, 97: 110-121.
12. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol, 1972, 32(3): 281-294.
13. Loscher W. Animal Models of seizures and epilepsy: past, present, and future role for the discovery of antiseizure drugs. Neurochem Res, 2017, 42(7): 1873-1888.
14. 劉陽, 韓春雷, 孟凡剛. 匹羅卡品癲癇模型研究進展. 中華神經外科雜志, 2014, 30(1): 88-90.
15. 陳樹達, 陳子怡, 方子妍, 等. 普朗尼克 P85 與維拉帕米對苯妥英鈉腦靶向分布的比較. 中山大學學報(醫學科學版), 2014, 35(2): 161-168.

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